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Safety and Efficacy of CAStem for Severe COVID-19 Associated With/Without ARDS

Primary Purpose

COVID-19, Acute Respiratory Distress Syndrome, Virus; Pneumonia

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CAStem
Sponsored by
Chinese Academy of Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring CAStem, Stem Cells, Cell Therapy, IMRCs

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  1. Chinese patients, aged 18 to 70 years old, males or females;
  2. Diagnosis of COVID-19, and confirm by chest CT scan;
  3. According to the diagnosis and treatment plan for the novel coronavirus disease (COVID-19) (trial version 5) issued by the National Health Commission (NHC) on the diagnostic criteria for severe or critical ill COVID-19 patients including the patients with acute respiratory distress syndrome (ARDS), the specific diagnostic criteria are:

    Severely ill patients should meet all of the following:

    • 1. Respiratory distress, RR ≥ 30 times/min.
    • 2. In a resting state (without oxygen supplementation), oxygen saturation ≤ 93%.
    • 3. Partial arterial oxygen pressure (PaO2) / oxygen absorption concentration (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kpa). High altitude (above sea level 1000 m) area should be calibrated for PaO2/FiO2 according to the following method: PaO2/FiO2*[atmospheric pressure (mmHg)/760]. Patients with obvious progress in lung lesions by chest CT within 24-48 hours should be counted as the server cases.

    Critically ill patients should meet one of the following :

    • 1. Respiratory failure, the mechanical ventilation required.
    • 2. Shock.
    • 3. Associated with other organ failure, ICU needed for monitoring and management.
  4. Voluntarily participate in the study, agree to comply with the requirements of the clinical trial protocol, and sign the informed consent.

Exclusion criteria:

  1. Patients with a history of transplantation of cells or organ(s).
  2. Patients with a history of malignancy or pathology indicating severe atypical hyperplasia.
  3. Patients without life expectancy of 48 hours.
  4. Patients with moderate to severe liver failure (Childs Pugh scores > 12).
  5. Patients with cardiogenic pulmonary edema.
  6. Patients with a history of deep vein thrombosis or pulmonary embolism within 3 months before the screening.
  7. Patients with severe chronic pulmonary diseases, including but not restricted to the patients with WHO grade III or IV pulmonary hypertension or those with chronic pulmonary diseases requiring long-term oxygen therapy.
  8. Patients with unstable ventricular tachycardia or ventricular fibrillation.
  9. Patients with poor coagulation, severe bleeding tendency or active bleeding at present.
  10. Patients with serious dysfunction involved in the major organs or systems (liver, kidney, gastrointestinal, cardiovascular, blood coagulation, central system, etc.) besides the respiratory system are not suitable to participate in the present study.
  11. Patients with a history of severe conditions in any organs or systems.
  12. Patients who are unable to accept other invasive rescue except cardiopulmonary resuscitation.
  13. Patients who are allergic to the main active ingredients or excipients of the investigational drug.
  14. Women who are pregnant, breastfeeding or planning to become pregnant during the study period. Woman of childbearing age who is not willing to use appropriate contraceptive methods through the completion of the clinical study.
  15. Patients whose participation is considered to bring significant risks to the present clinical study, cause confusion in analysis, or significantly interfere with the clinical research results.

Sites / Locations

  • Beijing YouAn Hospital, Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAStem

Arm Description

A dose-escalation with 3 cohorts with 3 patients/cohort who receive doses of 3, 5 or 10 million cells/kg. If there is no safety concerns for each cohort, the dose will be escalated from lower dose to next higher dose.

Outcomes

Primary Outcome Measures

Adverse reaction (AE) and severe adverse reaction (SAE)
Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment
Changes of lung imaging examinations
Evaluation by chest CT

Secondary Outcome Measures

Time to SARS-CoV-2 RT-PCR negative
Marker for SARS-CoV-2
Duration of fever (Celsius)
The duration of a fever above 37.3 degrees Celsius
Changes of blood oxygen (%)
Marker for efficacy
Rate of all-cause mortality within 28 days
Marker for efficacy
Lymphocyte count (*10^9/L)
Counts of lymphocyte in a litre (L) of blood
Alanine aminotransferase (U/L)
Alanine aminotransferase in unit (U)/litre(L)
Creatinine (umol/L)
Creatinine in micromole (umol)/litre(L)
Creatine kinase (U/L)
Creatine kinase in U/L
C-reactive protein (mg/L)
C-reactive in microgram (mg)/litre(L)
Procalcitonin (ng/L)
Procalcitonin in nanogram (ng)/litre(L)
Lactate (mmol/L)
Lactate in millimole(mmol)/litre(L)
IL-1beta (pg/mL)
IL-1beta in picogram(pg)/millilitre(mL)
IL-2 (pg/mL)
IL-2 in pg/mL
IL-6 (pg/mL)
IL-6 in pg/mL
IL-8 (pg/mL)
IL-8 in pg/mL

Full Information

First Posted
February 6, 2020
Last Updated
March 31, 2020
Sponsor
Chinese Academy of Sciences
Collaborators
Beijing YouAn Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04331613
Brief Title
Safety and Efficacy of CAStem for Severe COVID-19 Associated With/Without ARDS
Official Title
Safety and Efficacy Study of Human Embryonic Stem Cells Derived M Cells (CAStem) for the Treatment of Severe COVID-19 Associated With or Without Acute Respiratory Distress Syndrome (ARDS)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 27, 2020 (Actual)
Primary Completion Date
December 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Sciences
Collaborators
Beijing YouAn Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A phase1/2, open label, dose escalation, safety and early efficacy study of CAStem for the treatment of severe COVID-19 associated with or without ARDS.
Detailed Description
CAStem is an injectable product composed of immunity- and matrix-regulatory cells (IMRCs), also named M cells, differentiated from clinical-grade human embryonic stem cells (hESCs) will be expanded, harvested, and formulated at a concentration of 50 x 10^6 cells/mL. CAStem will be cryopreserved and transported to clinical site using liquid nitrogen vapor shipping vessels (< -150ºC). Prior to injection, CAStem will be thawed to liquefy quickly, and then reconstituted in normal saline.In the present study, the intravenous infusion dose of CAStem will be 3, 5 or 10 million cells/kg.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Acute Respiratory Distress Syndrome, Virus; Pneumonia, Acute Lung Injury
Keywords
CAStem, Stem Cells, Cell Therapy, IMRCs

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAStem
Arm Type
Experimental
Arm Description
A dose-escalation with 3 cohorts with 3 patients/cohort who receive doses of 3, 5 or 10 million cells/kg. If there is no safety concerns for each cohort, the dose will be escalated from lower dose to next higher dose.
Intervention Type
Biological
Intervention Name(s)
CAStem
Intervention Description
CAStem will be administered intravenously.
Primary Outcome Measure Information:
Title
Adverse reaction (AE) and severe adverse reaction (SAE)
Description
Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment
Time Frame
Within 28 days after treatment
Title
Changes of lung imaging examinations
Description
Evaluation by chest CT
Time Frame
Within 28 days after treatment
Secondary Outcome Measure Information:
Title
Time to SARS-CoV-2 RT-PCR negative
Description
Marker for SARS-CoV-2
Time Frame
Within 28 days after treatment
Title
Duration of fever (Celsius)
Description
The duration of a fever above 37.3 degrees Celsius
Time Frame
Within 28 days after treatment
Title
Changes of blood oxygen (%)
Description
Marker for efficacy
Time Frame
Within 28 days after treatment
Title
Rate of all-cause mortality within 28 days
Description
Marker for efficacy
Time Frame
Within 28 days after treatment
Title
Lymphocyte count (*10^9/L)
Description
Counts of lymphocyte in a litre (L) of blood
Time Frame
Within 28 days after treatment
Title
Alanine aminotransferase (U/L)
Description
Alanine aminotransferase in unit (U)/litre(L)
Time Frame
Within 28 days after treatment
Title
Creatinine (umol/L)
Description
Creatinine in micromole (umol)/litre(L)
Time Frame
Within 28 days after treatment
Title
Creatine kinase (U/L)
Description
Creatine kinase in U/L
Time Frame
Within 28 days after treatment
Title
C-reactive protein (mg/L)
Description
C-reactive in microgram (mg)/litre(L)
Time Frame
Within 28 days after treatment
Title
Procalcitonin (ng/L)
Description
Procalcitonin in nanogram (ng)/litre(L)
Time Frame
Within 28 days after treatment
Title
Lactate (mmol/L)
Description
Lactate in millimole(mmol)/litre(L)
Time Frame
Within 28 days after treatment
Title
IL-1beta (pg/mL)
Description
IL-1beta in picogram(pg)/millilitre(mL)
Time Frame
Within 28 days after treatment
Title
IL-2 (pg/mL)
Description
IL-2 in pg/mL
Time Frame
Within 28 days after treatment
Title
IL-6 (pg/mL)
Description
IL-6 in pg/mL
Time Frame
Within 28 days after treatment
Title
IL-8 (pg/mL)
Description
IL-8 in pg/mL
Time Frame
Within 28 days after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Chinese patients, aged 18 to 70 years old, males or females; Diagnosis of COVID-19, and confirm by chest CT scan; According to the diagnosis and treatment plan for the novel coronavirus disease (COVID-19) (trial version 5) issued by the National Health Commission (NHC) on the diagnostic criteria for severe or critical ill COVID-19 patients including the patients with acute respiratory distress syndrome (ARDS), the specific diagnostic criteria are: Severely ill patients should meet all of the following: 1. Respiratory distress, RR ≥ 30 times/min. 2. In a resting state (without oxygen supplementation), oxygen saturation ≤ 93%. 3. Partial arterial oxygen pressure (PaO2) / oxygen absorption concentration (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kpa). High altitude (above sea level 1000 m) area should be calibrated for PaO2/FiO2 according to the following method: PaO2/FiO2*[atmospheric pressure (mmHg)/760]. Patients with obvious progress in lung lesions by chest CT within 24-48 hours should be counted as the server cases. Critically ill patients should meet one of the following : 1. Respiratory failure, the mechanical ventilation required. 2. Shock. 3. Associated with other organ failure, ICU needed for monitoring and management. Voluntarily participate in the study, agree to comply with the requirements of the clinical trial protocol, and sign the informed consent. Exclusion criteria: Patients with a history of transplantation of cells or organ(s). Patients with a history of malignancy or pathology indicating severe atypical hyperplasia. Patients without life expectancy of 48 hours. Patients with moderate to severe liver failure (Childs Pugh scores > 12). Patients with cardiogenic pulmonary edema. Patients with a history of deep vein thrombosis or pulmonary embolism within 3 months before the screening. Patients with severe chronic pulmonary diseases, including but not restricted to the patients with WHO grade III or IV pulmonary hypertension or those with chronic pulmonary diseases requiring long-term oxygen therapy. Patients with unstable ventricular tachycardia or ventricular fibrillation. Patients with poor coagulation, severe bleeding tendency or active bleeding at present. Patients with serious dysfunction involved in the major organs or systems (liver, kidney, gastrointestinal, cardiovascular, blood coagulation, central system, etc.) besides the respiratory system are not suitable to participate in the present study. Patients with a history of severe conditions in any organs or systems. Patients who are unable to accept other invasive rescue except cardiopulmonary resuscitation. Patients who are allergic to the main active ingredients or excipients of the investigational drug. Women who are pregnant, breastfeeding or planning to become pregnant during the study period. Woman of childbearing age who is not willing to use appropriate contraceptive methods through the completion of the clinical study. Patients whose participation is considered to bring significant risks to the present clinical study, cause confusion in analysis, or significantly interfere with the clinical research results.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wang Liu, Doctor
Phone
+86-01064807858
Email
wangliu@ioz.ac.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Hao Jie, Doctor
Phone
+86-01062558737
Email
haojie@ioz.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhou Qi, Doctor
Organizational Affiliation
Institute of zoology, Chinese Academy of Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing YouAn Hospital, Capital Medical University
City
Beijing
State/Province
Beijing, China
ZIP/Postal Code
100000
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

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Safety and Efficacy of CAStem for Severe COVID-19 Associated With/Without ARDS

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